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The Journal of Neuroscience, August 1, 2002, 22(15):6781-6789
Two Time Periods of Hippocampal mRNA Synthesis Are Required for
Memory Consolidation of Fear-Motivated Learning
Lionel Muller
Igaz1,
Monica R. M.
Vianna3,
Jorge
H.
Medina1, 2, and
Ivan
Izquierdo3
1 Instituto de Biologia Celular y Neurociencias and
2 Departamento de Fisiologia, Facultad de Medicina,
Universidad de Buenos Aires, 1121 Buenos Aires, Argentina, and
3 Centro de Memoria, Departamento de Bioquimica,
Instituto de Biociencias, Universidade Federal de Rio Grande de Sul,
90035-003, Porto Alegre, Brazil
Information storage in the brain is a temporally graded process
involving different memory types or phases. It has been assumed for
over a century that one or more short-term memory (STM) processes are
involved in processing new information while long-term memory (LTM) is
being formed. It has been repeatedly reported that LTM requires
de novo RNA synthesis around the time of training. Here we show that LTM formation of a one-trial inhibitory avoidance training
in rats, a hippocampal-dependent form of contextual fear conditioning,
depends on two consolidation periods requiring synthesis of new mRNAs.
By injecting the RNA polymerase II inhibitors
5,6-dichloro-1- -D-ribofuranosylbenzimidazole or
 -amanitin into the CA1 region of the dorsal hippocampus at various
times before and after training, we found that hippocampal gene
expression is critical in two time windows: around the time of training
and 3-6 hr after training. Interestingly, these two periods of
sensitivity to transcriptional inhibitors are similar to those observed
using the protein synthesis inhibitor anisomycin. These findings
underscore the parallel dependence of LTM formation of contextual fear
on mRNA and protein synthesis in the hippocampus and suggest that the
two time periods of anisomycin-induced amnesia depend at least in part
on new mRNA synthesis.
Key words:
long-term memory; gene expression; hippocampus; rat; contextual fear; transcriptional inhibitors
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156781-09$05.00/0
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